1. Field of the Invention
This invention relates generally to medicament compositions for nasal administration of pharmacologically active peptides including Natrecor and Insulin, and more particularly to a unique such composition in a slightly moist form and for a system and method for administration of the composition.
2. Description of Related Art
Peptides such amino acid medications, Insulin, antibodies, recumbent DNA such as NATRECOR, stem cell preparations cannot be taken orally because the high acidic pH of the stomach destroys the medication activity. Therefore, such medications are traditionally administered by injection in combination with a transport media such as N-saline or N-glucose, insoluble solid suspensions as in the Reteculoendothyal (RE) system and an emulsion including insulin. Colloidal medical applications using the lung capillary as a bloodstream introduction mechanism are also becoming more widely accepted for introducing such peptides into the bloodstream.
A new form of insulin delivery without the need for injections has been developed by Generex Biotechnology Corporation in Toronto, Canada and is being marketed under the trade name ORALGEN. Oralgen is an Insulin formulation made for oral spray into the mouth by a special spray applicator carrying a trademark Rapid Mist Device. The insulin mist is thereby absorbed into the bloodstream through the mucous membranes in the mouth.
Prior U.S. patents provide an additional source for unique and distinctive compounds and techniques for administration of various newly developed drugs and pharmacologically active peptides.
U.S. Pat. No. 5,942,242 to Mizushima, et al. teaches a medicament for nasal administration for delivery of a vaccine or pharmacologically active peptide comprising a powder of one or more cation exchange resins to which a vaccine or pharmacologically active peptide is compounded. A novel insulin preparation, and more particularly an insulin preparation which is clinically suitable for nasal administration, is taught by Hirai, et al. in U.S. Pat. No. 4,153,689. Further limitations of this teaching relate to a failure to teach a true homogenous mixture which depends upon the mechanical binding of elements by VanDerVal-type binding which does not depend upon an ion exchange to effect transfer of the medicament into the nasal cavity.
A powdery pharmaceutical composition for nasal administration comprising a physiologically active polypeptide or its derivative and a water-absorbing, water-insoluble base is disclosed by Suzuki, et. al. in U.S. Pat. No. 4,613,500. U.S. Pat. No. 5,179,079 to Hansen, et. al. teaches a preparation for intranasal administration containing a pharmaceutically active polypeptide and an absorption enhancing system containing a fatty oil.
Illum is the inventor of seven (7) different U.S. patents directed to drug delivery compositions and formulations for nasal administration. U.S. Pat. No. 5,204,108 discloses a drug delivery composition comprising microspheres and an active drug while U.S. Pat. No. 5,629,011 teaches a composition for nasal administration of the polar metabolites of opioid analgesics. U.S. Pat. No. 5,648,095 teaches the preparation of microparticles and U.S. Pat. Nos. 5,707,644 and 5,804,212 are directed to small particle compositions for intranasal drug delivery. U.S. Pat. No. 5,690,954 discloses a drug delivery system containing microspheres, an active drug and a bioavailability improving material and U.S. Pat. No. 5,744,166 teaches drug delivery compositions.
Meezan, et al. in U.S. Pat. No. 5,661,130 teaches a method of increasing the absorption of a compound via the ocular, nasal, nasolacrimal or inhalation route into the circulatory system. A method of raising or lowering the blood glucose level by administering glucagon or insulin with absorption enhancers is further taught in '130.
Yanagawa discloses nasally administrable compositions in U.S. Pat. Nos. 5,603,943, 5,908,824, 6,197,328 and 6,589,559. The '943 patent teaches a nasally administrable composition with a physiologically active substance dispersed homogeneously in and onto a physiologically acceptable powdery or crystalline polyvalence metal compound carrier. The '824 patent teaches a composition containing a physiologically active peptide such as peptide hormone, physiologically active protein, enzymatic protein with a unique carrier that is highly absorbable into the body nasally. The nasally administrable composition of the '328 patent contains physiologically active compounds such as insulin, calcitonin, prostaglandin derivatives, monoclonal antibodies or interleukin derivatives. The '559 composition teaches a physiologically active substance dispersed homogeneously onto a fin powdery form of a cereal such as rice, wheat, soybean, corn, etc.
U.S. Pat. No. 5,997,848 to Patton, et al. teaches the delivery of insulin by inhalation of a dry powder form of insulin. A system and method for producing microparticles loaded with biologically active drugs for controlled release of the drugs in a nasal passageway is taught by Bomberger, et al. in U.S. Pat. No. 6,375,985.
A powdery nasal composition comprising a drug and colloidal cellulose is taught by Dohi, et al. in U.S. Pat. No. 6,428,805 and Vickery, et al., in U.S. Pat. No. 6,521,597 teaches intranasal administration of LHRH polypeptides in powdered form.
U.S. patent application Publication US 2002/0012688 A1 to Dohi, et al. discloses a powdery composition for nasal administration containing a drug, a water-absorbing base material such as hydroxypropyl cellulose and a water-absorbing and water-insoluble base material such as crystalline cellulose.
U.S. patent application Publication US 2004/0063615 A1 to Oki, et al. teaches an insulin-containing composition for nasal administration comprising a crystalline cellulose aggregate as a carrier.
European Patent EP0200383 invented by Campanale and Su, discloses a method for treatment of diabetes mellitus comprising a pharmaceutically acceptable amount of an alkali metal salt, or the free acid of a substantially zinc-free insulin in the presence of an absorption enhancing agent.
A formulation for nasal insulin delivery is further shown in the abstract of WO9422461 to Franciscus Merkus, as published in BE1006873 and AU6428994. Finally, WO 03/004048 A1 to Oki, et al. teaches granular compositions for nasal administration of insulin which comprise as a carrier aggregated crystalline cellulose.
Other compositions adapted for nasal administration are as follows:                U.S. Pat. No. 5,578,567 to Cardinaux, et al.        U.S. Pat. No. 5,725,852 to Igari, et al.        U.S. Pat. No. 5,948,749 to Igarashi, et al.        U.S. Pat. No. 6,416,742 to Stefely, et al.        U.S. Pat. No. 6,506,730 to Lee, et al.        U.S. Pat. No. 6,428,780 to Leone-Bay, et al.        U.S. Pat. No. 6,699,467 to Leone-Bay, et al.        U.S. Pat. No. 4,294,828 to Thominet, et al.        